BMC Seminar Thursday 13 February, 12:00 in Læknagarður, Vatnsmýrarvegur 16, room 343
Speaker: Dr. Valerie Fock, postdoctoral research fellow in Prof. Eiríkur Steingrímsson´s laboratory, Faculty of Medicine, University of Iceland.
Title: Novel aspects of MITF in melanoma
Abstract: Microphthalmia-associated transcription factor (MITF) is a member of the basic helix-loop-helix leucine zipper (bHLH-Zip) family and plays a key role in the establishment of the melanocytic lineage. Given its central role in melanoma and pigmentation disorders, proper characterization of MITF is required for advancing our understanding of the nature of these diseases. Over the past years, we have studied various aspects of MITF, including its subcellular localization and stability, interaction partners and post-translational modifications. By using EGFP fusions and in vitro mutagenesis, we identified three conserved karyophilic signals in the bHLH-Zip domain of MITF, which orchestrate the transcription factor’s nuclear localization. Importantly, variants in a number of the residues involved have been associated with Waardenburg syndrome type 2A and Tietz syndrome. Furthermore, we showed that dimerization is crucial for MITF stability in cells of the melanocytic lineage. Together with our collaborators, we have recently mapped the interactome of MITF in the chromatin, nuclear and cytoplasmic compartments of melanoma cells. Based on these data and the use of a transactivation-incompetent MITF mutant, we were able to define a transcription-independent function for MITF in autophagy. Last but not least, by pursuing a targeted proteomic approach, we have characterized the phosphorylation status of MITF in the context of BRAF mutant melanoma and are currently assessing the functional effects of these modifications on MITF activity and melanoma cell phenotypes.
Biosketch: Valerie Fock obtained her PhD degree at the Medical University of Vienna in 2015, where she studied the role of interleukin-1 family members during trophoblast development. For her postdoctoral training, she received an Erwin Schrödinger Fellowship to join the lab of Prof. Eiríkur Steingrímsson at the University of Iceland. Her research interests focus on the MiT/TFE family of transcription factors in melanoma.